Thaum cov kab mob ua rau tib neeg lub neej txaus ntshai, nws tseem ceeb heev kom paub tias cov tshuaj tiv thaiv kab mob ua haujlwm li cas.GS-441524 hmoovtau dhau los ua qhov muaj txiaj ntsig zoo ntawm nucleoside mimic uas txwv cov kab mob los ntawm kev luam lawv tus kheej los ntawm kev tawm tsam cov txheej txheem yooj yim: RNA synthesis. Vim li no, nws ua haujlwm zoo tshwj xeeb tshaj yog tiv thaiv kab mob RNA zoo li tus mob coronaviruses thiab feline infectious peritonitis virus (FIPV).
GS-441524 hmoov muaj zog heev vim nws tuaj yeem zoo li cov nucleotides ntuj thaum tiv thaiv cov kab mob los ntawm kev ua cov khoom uas lawv xav tau kom loj hlob. Cov tshuaj no txwv tsis pub tsim cov kab mob ntawm qib molecular los ntawm kev thaiv cov kab mob RNA-dependent RNA polymerase (RdRp) thiab xaus chains sai dhau. Ntau hom kab mob viral tau pom tias muaj txiaj ntsig zoo hauv kev tshawb fawb, uas ua rau nws xaiv zoo rau cov tsiaj thiab tib neeg siv tau.
Cov kws tshawb fawb, kws muag tshuaj, thiab kws kho tsiaj tuaj yeem nkag siab zoo txog qhov kev kho mob no los ntawm kev nkag siab tias nws txwv kev tsim cov kab mob RNA li cas. Peb yuav saib kom meej ntxiv seb GS-441524 hmoov ua haujlwm li cas los tua cov kab mob hauv qhov chaw uas ua raws.
GS-441524 Fp
1. General Specification (hauv Tshuag)
(1) Txhaj tshuaj
20 mg, 6 ml; 30 mg, 8 ml; 40 mg, 10 ml
(2) Tablet
25/45/60/70 mg tab
(3) API (Ntshiab hmoov)
(4) Pill press machine
https://www.achievechem.com/pill-xwm
2.Customization:
Peb yuav sib tham tus kheej, OEM / ODM, Tsis muaj hom, rau kev tshawb nrhiav kev ruaj ntseg nkaus xwb.
Tus Qauv Zauv: BM-1-001
GS-441524 CAS Nr .: 1191237-69-0
Kev tshuaj xyuas: HPLC, LC-MS, HNMR
Lub khw tseem ceeb: Tebchaws Asmeskas, Australia, Brazil, Nyiv, Lub Tebchaws Yelemees, Indonesia, UK, New Zealand, Canada thiab lwm yam.
Peb muabGS-441524 IB, thov xa mus rau lub vev xaib hauv qab no kom paub meej specifications thiab cov ntaub ntawv khoom.
Khoom siv:https://www.bloomtechz.com/synthetic-chemical/api-kev tshawb nrhiav-only/gs-441524-fip.html
Yuav ua li cas GS -441524 Powder Targets RNA-Dependent RNA Polymerase
Lub luag haujlwm tseem ceeb ntawm RdRp hauv Viral Replication
Cov kab mob RNA replicate lawv cov khoom siv caj ces ntawm RNA-nyob ntawm RNA polymerase. Cov kab mob RNA muaj lawv tus kheej RdRp enzyme, tsis zoo li cov kab mob DNA thiab cov hlwb nyob. Cov enzyme no nyeem cov kab mob RNA cov qauv thiab tsim cov strands ntxiv. Qhov no tso cai rau tus kab mob rov ua dua nws cov genome hauv cov kab mob.
RdRp feem ntau tsis pom muaj nyob hauv cov tswv tsev, yog li cov tshuaj tua kab mob tuaj yeem ua haujlwm tau zoo. Vim li no, cov tshuaj uas lub hom phiaj RdRp tuaj yeem tua tus kab mob yam tsis muaj kev puas tsuaj rau cov txheej txheem ntawm tes. Lub enzyme ntxiv nucleotides los tsim RNA chains ntawm nws qhov chaw nquag. Qhov no yog qhov tseem ceeb rau kev kis tus kab mob.
Molecular Mimicry Strategy
Lub intricate tshuaj mimicry ntawm GS-441524 hmoov fools viral polymerase los ntawm mimicking ntuj adenosine nucleotides. Nws hloov pauv cov piam thaj molecule thiab nucleobase tso cai rau nws nkag mus rau RdRp qhov chaw nquag.
Hauv cov hlwb mob, GS-441524 yog phosphorylated los ua kom muaj zog triphosphate. Raws li tus kab mob RNA kab mob loj hlob, ntuj ATP thiab daim ntawv triphosphate no sim ua ke. Vim nws cov qauv zoo sib xws, RdRp yuav yuam kev GS-441524 triphosphate rau lub hauv paus.
Kev sib tw Inhibition Dynamics
Zoo li kev sib tw sib tw, GS-441524 hmoov metabolites thiab RdRp cuam tshuam. RNA yog tsim los ntawm polymerase xaiv nucleotides los ntawm lub cell lub khw raws li hauv paus kev sib koom ua ke. GS-441524 triphosphate sib tw nrog ATP niaj hnub no.
Tus kab mob RdRp tuaj yeem nqus GS-441524 triphosphate, txawm tias tsis zoo li nucleotides ib txwm, raws li kev ntsuas kev sib raug zoo.
Kev ua tau zoo nyob ntawm seb cov tshuaj metabolite ntau npaum li cas tam sim no txheeb ze rau cov nucleotides ntuj vim qhov kev sib tw sib tw.Cells nrog ntau dua GS-441524 muaj feem cuam tshuam rau kev sib xyaw ua ke rau hauv cov kab mob RNA.
Tus kab mob RdRp ntawd yog xaiv ntau dua li cov cellular polymerases, uas ua rau peb muaj kev nyab xeeb tseem ceeb hauv ncoo. Kev tshawb fawb qhia tau hais tias cov kab mob enzymes nqus GS-441524 hmoov khoom zoo dua tib neeg DNA lossis RNA polymerases. Qhov no pab txhawb rau nws qhov zoo tshaj plaws tshuaj index.
RNA Chain Termination Mechanisms ntawm GS-441524 Hmoov
Delayed Chain Termination Approach
GS-441524 hmoovsiv txoj kev ncua ncua, uas txawv ntawm lwm cov nucleoside tebchaw uas xaus cov saw tam tam sim ntawd. Cov polymerase tseem tuaj yeem ntxiv ob peb nucleotides ntxiv rau cov saw hlau ua ntej nws tsis loj hlob tom qab RdRp ntxiv GS-441524 rau RNA strand loj hlob. Cov nyhuv no tshwm sim tom qab vim tias cov piam thaj hloov pauv tsis ua tiav qhov kev tshwm sim tom ntej ntawm kev suav nrog.
Kev txiav tawm feem ntau tshwm sim peb mus rau tsib nucleotides tom qab GS-441524 qhov taw qhia, raws li kev tshawb fawb.
Cov qauv ncua sij hawm no cuam tshuam cov kab mob tiv thaiv los ntawm kev ua yuam kev - xyuas cov txheej txheem. Qee cov kab mob polymerases 'exonuclease proofreading muaj peev xwm nrhiav tsis tau thiab tshem tawm cov ntawv luam ntxiv ua ntej txiav.
Kev cuam tshuam kev cuam tshuam ntawm Viral RNA
Qhov kawg ncua sij hawm kuj tso cai rau ntau GS-441524 hmoov khoom molecules los koom nrog ib RNA strand, ua rau replication tsis ua hauj lwm. Txhua qhov kev sib koom ua ke tuaj yeem tso tseg, ua rau muaj kev cuam tshuam tsis zoo uas tshwm sim.Thaum GS-441524 txuas tus kab mob RNA, nws hloov cov qauv, cuam tshuam rau cov txheej txheem hauv qab. Qhov hloov pauv nucleoside hloov pauv RNA cov duab hauv zos, uas tuaj yeem cuam tshuam nws qhov folding, ruaj khov, thiab ua haujlwm.
Viral RNA yuav tsum yog peb - qhov ntev kom ua raws li cov protein txhais lus thiab rov ua dua.
Ntxiv GS-441524 residues tuaj yeem cuam tshuam cov qauv tseem ceeb no. Vim lub C-nucleoside qauv thiab kev ua haujlwm pab pawg tso, hluavtaws thiab ntuj adenosine sib txawv me ntsis tseem ceeb. Cov kev hloov pauv ntawm cov qauv no tuaj yeem cuam tshuam li cas RNA cuam tshuam nrog cov kab mob thiab cov cellular proteins tseem ceeb rau tus kab mob lub neej.
Biochemical Consequences rau Viral Assembly
GS-441524 hmoov derivatives yuav hloov RNA strand stability.
Qee qhov kev tshawb fawb pom tias cellular RNases rhuav tshem cov hloov pauv RNAs sai dua, txo qhov ua haujlwm ntawm cov kab mob kis tau zoo. Hauv ntau qhov kev hwm, qhov kev hloov pauv no ntxiv dag zog rau kev tiv thaiv kab mob dhau ntawm kev sib tsoo.Ua tus kab mob RNA uas raug txiav tawm thiab ua tsis zoo cuam tshuam rau cov kab mob sib dhos. Cov kab mob yuav tsum tau koom ua ke tag nrho -ntev genetic RNA los tsim cov khoom tshiab. Cov kab mob tsis kis tau vim tsis tiav RNA genomes tsis tuaj yeem qhia lub xov tooj ntawm tes yuav ua li cas los tsim tag nrho cov kab mob sib kis.
GS-441524 tuaj yeem ua rau qee qhov ntev RNA tsis muaj txiaj ntsig txawm tias nws tseem muaj txoj sia nyob. Cov kab mob sib kis tau yooj yim tuaj yeem txhim kho nyob ib puag ncig cov qauv tsis zoo no, nkim cov peev txheej ntawm tes yam tsis muaj kev noj qab haus huv progeny. Tus kab mob no tsis kis tus kab mob vim nws nyob ruaj khov.
Thaum cov mob hlwb raug kho nrog GS-441524 hmoov, cov kab mob kis kab mob ntau zuj zus zuj zus. Kev sib piv txhim khu kev qha ntawm cov kab mob hauv cov hlwb uas kho thiab tsis kho tau pom ntau qhov kev poob qis. Kev txwv tsis pub RNA ntau lawm ua rau cov tshuaj muaj txiaj ntsig tshwj xeeb hauv kev tua kab mob.
Vim li cas Viral RNA Synthesis tseem ceeb rau Coronavirus Replication
Kev Yuav Tsum Tau Ua Tsis Taus
Zoo li lwm yam kab mob RNA, tus mob coronaviruses tsis tuaj yeem koom nrog tus tswv tsev DNA thiab yuav tsum tau ua kom RNA tshiab kom kis tau tus mob. Tus kab mob coronavirus ua rau nws qhov zoo -sens RNA genome thaum nws nkag mus rau hauv lub cell. Qhov RNA no ua tus xa xov rau thawj cov protein synthesis. Ib feem ntawm qhov rov ua dua-txoj kev hloov pauv, xws li RdRp, yog qee yam ntawm thawj cov proteins uas tau tsim.Qhov kev rov ua dua tshiab no ua rau ntawm daim nyias nyias hauv cov hlwb thiab pib ua qhov tsis zoo -xav RNA templates los ntawm genomic RNA.
Tom qab ntawd, qhov zoo dua -sens genomic RNA thiab subgenomic RNAs yog tsim los ntawm cov tsis zoo no -sens intermediates. Cov subgenomic RNAs code rau cov qauv thiab cov khoom siv ntxiv uas xav tau los ua cov kab mob.
Qhov kev tsim RNA tas li no yog qhov tsim nyog rau tag nrho lub neej ntawm tus kabmob coronavirus. Thaum tsis ua haujlwm RdRp kev ua haujlwm, tus kab mob tsis tuaj yeem luam nws cov khoom siv caj ces, ua kom muaj cov kab mob txaus ntshai, lossis ua luam tawm ntawm nws tus kheej. Vim li no, RNA synthesis yog Achilles 'pob txhaGS-441524 hmoovsiv qhov zoo.
High Mutation Rate thiab Replication Fidelity
RNA tus kab mob polymerases feem ntau tsis muaj zog kho tshuab, uas txhais tau hais tias muaj ntau qhov kev hloov pauv thaum rov ua dua. Coronaviruses txawv ntawm lwm cov kab mob RNA vim tias lawv muaj 3'-5' exonuclease (ExoN) uas kho qhov yuam kev thiab ua kom rov ua dua tshiab dua. Qhov kev ua exonuclease no tuaj yeem ua rau cov kab mob ua rau cov tshuaj tiv thaiv kab mob.
Thaum xub thawj, qhov tshwm sim ntawm ExoN ua rau tib neeg txhawj xeeb txog kev hloov pauv nucleoside tsis ua haujlwm zoo li. Qee qhov kev tshawb fawb pom tias tus mob coronaviruses nrog kev ua haujlwm ExoN tuaj yeem tshem tawm cov tshuaj analogues, uas yuav ua rau cov tshuaj tsis zoo.
GS-441524 hmoov thiab nws niam nws txiv cov khoom, Remdesivir, tau siv nyob rau hauv cov kev tshawb fawb uas qhia tau hais tias lub ncua sij hawm txoj kev txiav mechanism pab tau ib ncig ntawm no mechanism.
Ntau RNA Synthesis cov kauj ruam ua cov ntsiab lus cuam tshuam
Thaum GS-441524 raug faus rau hauv RNA strand thiab ntxiv nucleotides ntxiv rau hauv qab, cov exonuclease tsis tuaj yeem tshem nws yooj yim. Txoj kev ncua ncua sij hawm ua tau zoo dua tiv thaiv tus mob coronaviruses dua li tam sim-terminator nucleoside analogues, uas tej zaum yuav yooj yim dua tshem tawm.
Coronavirus RNA synthesis muaj ntau theem, txhua qhov uas tej zaum yuav raug siv.Ua tsis zoo -sensitive templates txawv ntawm kev ua genomic-ntev zoo- hnov RNA thiab subgenomic mRNAs. Tag nrho cov txheej txheem no cia siab rau tib lub RdRp enzyme; GS-441524 hmoov tuaj yeem ntsia lawv.
Cov tshuaj ua haujlwm zoo tshaj plaws thaum lub sijhawm nthuav dav, thaum tus kab mob tsim ntau RNA luam tawm sai. Nyob rau ntawm no, inhibiting txawm me ntsis RNA ntau lawm yuav txo tau tus kab mob hnyav.
Cov tshuaj concentration thiab kev tiv thaiv kab mob tsis tshua muaj sib cuam tshuam linearly. Yog li, kev hloov kho me me ntawm cov tshuaj yuav ua rau muaj kev tiv thaiv kab mob ntau ntxiv. Kev zam RNA synthesis tseem tiv thaiv cov kab mob kis kab mob los ntawm kev zais ntawm lub cev tiv thaiv kab mob. Ntau tus mob coronaviruses tsim cov proteins uas thaiv kev tiv thaiv tus tswv xws li interferon. GS-441524 hmoov tiv thaiv tus kab mob los ntawm kev tsim cov kev tiv thaiv no los ntawm kev cuam tshuam RNA synthesis thaum ntxov, uas tuaj yeem txhawb tus tswv tsev tiv thaiv kab mob.
Intracellular Activation Pathways ntawm GS-441524 hmoov
Cellular Kinase Phosphorylation Cov kauj ruam
GS-441524 hmoov nkag mus rau hauv hlwb raws li ib tug prodrug uas yuav tsum tau activated metabolically ua ntej nws yuav tua tau cov kab mob. Txhawm rau ua kom cov active triphosphate molecule, cov tshuaj yuav tsum mus dhau peb kauj ruam ntawm phosphorylation, uas yog sped los ntawm cellular kinases. Cov txheej txheem ua haujlwm no yog ob qho tib si tsim nyog rau cov tshuaj ua haujlwm thiab tuaj yeem ua rau nws tsis zoo.
GS-441524 hloov mus rau nws daim ntawv monophosphate hauv thawj kauj ruam ntawm phosphorylation. Qhov thawj phosphorylation no tau pom tias ua rau qeeb ntawm cov txheej txheem hauv qee hom hlwb.
Sib txawv cellular kinases tsis zoo li nrhiav thiab phosphorylating GS-441524 li lwm tus. Qhov no yuav piav qhia tias yog vim li cas cov xov tooj ntawm tes thiab lub cev sib txawv tsis muaj txiaj ntsig zoo ntawm kev tua kab mob.
Cellular Uptake thiab Distribution
Phosphorylation rau diphosphate thiab triphosphate cov ntaub ntawv ua raws sai dua. Nucleoside monophosphate thiab diphosphate kinases pab qhov no. Cov enzymes no khaws ntau cov substrate. Tom qab tsim, GS-441524 triphosphate khaws cov tshuaj tiv thaiv kab mob hauv cov hlwb.
Yuav ua li cas zooGS-441524 hmoovnkag mus rau hauv hlwb txiav txim nws cov tshuaj. Raws li ib tug nucleoside analogue, GS-441524 yuav passively traverse cell membranes vim nws cov lipophilicity me ntsis.Nucleoside transporters yog protein raws uas pab natural nucleosides nkag mus thiab tawm hlwb. Cov no yuav siv tau los ntawm cov tshuaj.
Kev tshawb fawb txog yuav ua li cas cov hlwb nqus GS-441524 qhia tias nws tuaj yeem ncav cuag qib kho mob ntawm cov tshuaj noj. Cov molecule nyob rau hauv ntau cov ntaub so ntswg pab kho cov kab mob uas kis thoob plaws lub cev. Thaum cov tib neeg txaus nkag mus rau thaj chaw nyab xeeb uas cov kab mob tuaj yeem nyob, kev tswj kab mob yooj yim.
Metabolic Stability thiab tshem tawm
Ntau npaum li cas los tswj GS-441524 hmoov triphosphate nyob ntawm nws lub cell ib nrab-lub neej. Triphosphate tseem nyob hauv hlwb rau lub sijhawm ntev, tswj cov tshuaj tiv thaiv kab mob thaum cov ntshav plasma poob qis, raws li kev tshawb fawb. Kev siv tshuaj kho mob tau zoo yog qhov ua tiav vim yog tus yam ntxwv ntawm cov tshuaj pharmacokinetic.Kev nkag siab yuav ua li cas GS-441524 hmoov metabolised txhim kho txoj hauv kev kho mob. Cov molecule tau hloov pauv cov metabolism dhau phosphorylation mus rau cov metabolites nquag.Cellular enzymes deaminate, oxidise, los yog sib xyaw GS-441524, tsim cov tshuaj tsis muaj zog uas lub raum ntxuav tawm.
Qhov sib npaug ntawm kev ua kom muaj zog thiab tshem tawm txoj hauv kev txiav txim siab ntawm tes - qib tshuaj lom neeg. Cov neeg mob sib txawv tuaj yeem teb txawv yog tias cellular kinases lossis metabolising enzymes hloov. Vim tias cov metabolism tsis yooj yim, kev saib xyuas cov tshuaj kho mob yuav pab tau qee cov neeg mob tau txais kev kho kom zoo.GS-441524 hmoov thiab nws cov metabolites feem ntau yog tshem tawm ntawm lub raum. Cov neeg lossis cov tsiaj uas muaj lub raum tsis ua haujlwm yuav muaj cov tshuaj pharmacokinetics sib txawv, yuav tsum tau hloov kho koob tshuaj. Paub tias cov tshuaj raug tshem tawm li cas pab koj xaiv cov koob tshuaj kom zoo thiab kwv yees seb lawv yuav cuam tshuam li cas nrog rau lwm yam kev thauj mus los rau lub raum lossis cov tshuaj metabolism.
Broad RNA Virus Inhibition Research Nrog GS-441524 Hmoov
Kev Tawm Tsam Tawm Tsam Ntau Tsev Neeg Viral
Cov kws tshawb fawb tau pom tias GS-441524 hmoov muaj txiaj ntsig tiv thaiv ntau tsev neeg tus kab mob RNA ntxiv rau tus kabmob coronaviruses. Kev tshawb fawb hauv chav kuaj pom tias nws tuaj yeem tua cov kab mob flaviviruses, filoviruses, paramyxoviruses, thiab lwm yam kab mob RNA. Qhov sib xyaw ua ke muaj ntau yam teebmeem los ntawm nws lub peev xwm los tsom RdRp, ib qho enzyme uas muaj nyob hauv txhua tsev neeg tus kab mob RNA.
Cov kab mob sib txawv muaj qib sib txawv ntawm qhov ua tau zoo ntawm cov tshuaj tiv thaiv kab mob.
Qee yam uas cuam tshuam rau nws ua haujlwm tau zoo npaum li cas yog cov pleev ntawm txhua tus kab mob RdRp, GS zoo npaum li cas -441524 phosphorylates hauv cov hom phiaj hlwb, thiab ceev npaum li cas tus kab mob replicates. Cov tshuaj tiv thaiv teb tau pom EC50 qhov tseem ceeb (cov koob tshuaj uas nres tus kab mob hauv ib nrab ntawm lub sijhawm) rau ntau hom.
Kev Tshawb Fawb Txog Kev Tshawb Fawb
Nrog submicromolar EC50 qhov tseem ceeb, GS-441524 hmoov muaj cov haujlwm tseem ceeb FIPV. Qhov kev ua haujlwm muaj zog no tau kho tau zoo kawg nkaus feline kis kab mob peritonitis, ib qho mob txaus ntshai. Tib neeg xav siv cov thev naus laus zis no los kho cov kab mob ntxiv vim nws ua haujlwm hauv cov tsiaj.
Sib piv GS-441524 hmoov rau lwm cov tshuaj tiv thaiv kab mob nucleoside pab piav qhia nws cov txiaj ntsig. Kev sim ntau yam tshuaj tiv thaiv tib lub hom phiaj kab mob qhia lawv qhov zoo thiab qhov tsis muaj zog. Feem ntau, GS-441524 muaj txiaj ntsig zoo dua lossis muaj txiaj ntsig ntau dua li cov tshuaj tiv thaiv yav dhau los.
GS-441524 thiab Remdesivir yuav tsum tau saib xyuas zoo. Remdesivir, ib tug prodrug, hloov mus rau hauv GS-441524 monophosphate nyob rau hauv lub hlwb, zam lub sluggish thawj theem phosphorylation. Remdesivir ua haujlwm zoo dua hauv kab lis kev cai ntawm tes vim qhov kev hloov kho no.
Ob yam tshuaj tsim tus kab mob - tua triphosphate molecule. Remdesivir absorbs ntau triphosphate mus rau hauv cov hlwb ntawm tib lub extracellular theem, txawm hais tias GS-441524 hmoov yog superior nyob rau hauv tej rooj plaub, raws li cov kws tshawb fawb. GS-441524 yog ruaj khov dua, yooj yim rau synthesis, thiab tej zaum yuav pheej yig dua los tsim vim nws cov qauv tshuaj yooj yim, ua rau nws yooj yim dua thiab muaj txiaj ntsig.
Resistance Monitoring thiab Mechanism Studies
Cov tshuaj tua kab mob yuav tsum xav txog kev pheej hmoo ntawm tus kab mob no. Serial passage kev tshawb fawb, nyob rau hauv uas cov kab mob ntau zaus thaum cov tshuaj yog tam sim no, tau siv los kawm GS-441524 hmoov kam rau ua.
Qhov kev tshawb fawb no nrhiav cov noob uas txo cov tshuaj tua kab mob.Cov ntaub ntawv qhia tau tias GS-441524 tsim kev kam rau siab qeeb dua lwm cov tshuaj tiv thaiv kab mob. Kev hloov kho kuj tseem tshwm sim hauv RdRp gene, hloov kho cov amino acids ze ntawm lub enzyme. Kev hloov pauv tuaj yeem ua rau GS-441524 triphosphate nyuaj rau kev sib xyaw lossis yooj yim dua rau cov exonuclease tshem tawm.
Kev hloov kho kev tiv thaiv muaj tus nqi qoj ib ce, yog li tshuaj - cov kab mob tiv thaiv ua rau lawv tus kheej tsis zoo. Raws li qhov kev tshawb fawb no, cov kab mob tiv taus yuav tsis tuaj yeem tshem tawm sai sai ntawm cov kab mob uas muaj kab mob hauv cov tsiaj qus. Ua keGS-441524 hmoovnrog rau lwm cov tshuaj tiv thaiv kab mob tuaj yeem txo qhov tsis kam.
Kev txiav txim siab txog kev txhais lus kho mob
Txhawm rau txhais cov tshuaj tiv thaiv kab mob vitro rau hauv kev kho mob ua tiav, ntau qhov sib txawv yuav tsum tau hais. Kev tshawb fawb tsiaj yog qhov tseem ceeb rau kev ua pov thawj tias GS-441524 hmoov tuaj yeem ncav cuag cov tshuaj kho mob hauv cov kab mob thiab muaj txiaj ntsig kho mob. Cov kws kho tsiaj uas tau kho cov miv nrog FIP tuaj yeem tham txog kev nyab xeeb, kev ua tau zoo, thiab kev siv.
Cov ntawv thov kev kho tsiaj no qhia tib neeg tej yam tseem ceeb. Kev kho lub sij hawm, zaus, thiab pib thaum ntxov muaj feem cuam tshuam. Thaum ntxov -FIP miv feem ntau yuav kho tau. Qhov no qhia txog qhov xav tau kev kuaj mob ntxov thiab kev kho mob.
Tom qab nws cov txiaj ntsig zoo nrog FIP, GS-441524 hmoov raug txiav txim siab rau lub hom phiaj ntxiv. Kev tshawb fawb dav dav suav nrog kev tswj hwm txoj hauv kev, kev lag luam scale-up, thiab kev lag luam. Muaj zog tiv thaiv kab mob thiab nthuav cov ntaub ntawv kev nyab xeeb ua rau cov tshuaj muaj txiaj ntsig zoo hauv kev sib ntaus sib tua tiv thaiv kab mob RNA.
Xaus
GS-441524 hmoov muaj ntau yam tshuaj tiv thaiv kab mob uas tiv thaiv kab mob los ntawm kev tsim RNA. Cov tshuaj no ua haujlwm zoo li cov nucleosides ntuj, sib tw nrog tus kab mob RdRp rau kev suav nrog thiab ncua cov saw hlau txiav kom txwv tsis pub kis kab mob. Los ntawm kev tsim tus kab mob RNA uas tsis ua haujlwm, suav nrog cov txheej txheem cuam tshuam txhawb kev tiv thaiv kab mob.
Nws lub peev xwm los tawm tsam tus kabmob coronaviruses thiab FIPV qhia nws lub peev xwm los tsom RNA synthesis. Lub ncua sij hawm kawg mechanism tsis txhob kis tus kab mob proofreading kuj, ncua nws lifespan. Cells phosphorylate prodrug rau hauv nws daim ntawv active triphosphate. Daim ntawv no tsim nyob rau hauv cov kab mob hlwb kom tswj tau cov tshuaj tiv thaiv kab mob siab.
Yog tias cov kws tshawb fawb, kws kho mob, thiab cov neeg ua haujlwm kho mob nkag siab txog cov tshuaj no, lawv tuaj yeem siv GS-441524 hmoov zoo. Qhov sib xyaw ua haujlwm hauv cov tshuaj tsiaj qhia txog kev kho mob los ntawm kev tso tseg RNA synthesis. Txhawm rau tswj hwm tus kab mob no muaj txiaj ntsig zoo tiv thaiv tus kab mob tshwm sim, kev tshawb fawb txuas ntxiv yog tshawb nrhiav cov ntawv thov tshiab, txhim kho cov tswv yim kho mob, thiab saib xyuas kev txhim kho kev tiv thaiv.
FAQ
1. Dab tsi ua rau GS-441524 hmoov zoo tiv thaiv kab mob RNA?
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GS-441524 hmoov ua haujlwm vim nws muaj cov qauv nucleoside analogue uas zoo ib yam li ntuj adenosine. Nws sib tw nrog cov nucleotides ntuj rau kev suav nrog rau tus kab mob RNA los ntawm RdRp tom qab raug coj los ntawm cov hlwb thiab phosphorylated rau daim ntawv active triphosphate. Thaum nws tau ntxiv lawm, nws ncua sijhawm kawg ntawm cov saw hlau, cuam tshuam cov qauv ntawm RNA, thiab nres kev tsim cov kab mob ua haujlwm genomes. Cov txheej txheem ntau yam no muaj cov tshuaj tua kab mob muaj zog tiv thaiv ntau hom kab mob RNA, tab sis nws ua haujlwm tshwj xeeb tshaj yog tiv thaiv tus mob coronaviruses thiab FIPV.
2. Yuav ua li cas lub sij hawm ncua sij hawm ntawm kev txiav tawm mechanism ua haujlwm?
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Hloov chaw nres RNA synthesis tam sim ntawd zoo li feem ntau cov saw terminators ua, GS-441524 hmoov cia cov kab mob polymerase ntxiv peb mus rau tsib ntxiv nucleotides tom qab suav nrog ua ntej kev txiav tawm. Qhov sib xyaw ua ke ntawm cov qauv qab zib hloov ua rau qhov kev ncua qeeb, tab sis nws tsis ua tiav qhov kev sib koom ua ke tom ntej. Qhov ncua sij hawm ua rau nws nyuaj rau tus kab mob kho cov enzymes kom pom thiab tshem tawm cov analog ntxiv, uas yuav pab tau ib puag ncig cov txheej txheem tiv thaiv. Ntau GS-441524 molecules tuaj yeem koom ua ke los tsim ib qho RNA strand, uas ua rau kom muaj feem cuam tshuam.
3. Vim li cas GS-441524 hmoov tshwj xeeb tshaj yog tiv thaiv tus mob coronaviruses?
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Coronaviruses tsis tuaj yeem rov ua dua yam tsis tas RNA synthesis, uas yog vim li cas thaiv RdRp yog qhov phem heev rau lawv lub neej voj voog. Coronaviruses muaj exonuclease proofreading ua si uas tej zaum yuav tau tshem ntawm nucleoside analogues uas tau ntxiv, tab sis GS-441524 hmoov lub ncua sij hawm txiav mechanism tau txais nyob ib ncig ntawm no kev tiv thaiv. Cov tshuaj nres tag nrho cov kauj ruam ntawm tus mob coronavirus RNA ntau lawm, xws li kev tsim cov qauv tsis zoo -sensitive templates, qhov nce ntawm genomic RNA, thiab tsim cov subgenomic mRNA. Cov tshuaj tiv thaiv kab mob muaj zog pom nyob rau hauv ob qho tib si hauv chaw kuaj mob thiab chaw kho mob yog tshwm sim los ntawm qhov kev tawm tsam tag nrho, nrog rau kev siv cellular zoo thiab ua kom muaj zog.
Koom Tes Nrog BLOOM TECH rau hwm GS-441524 hmoov khoom
BLOOM TECH yog qhovGS-441524 hmoovtus kws kho mob koj tuaj yeem ntseeg tau muab tshuaj rau koj - cov ntaub ntawv qib uas tau txais kev lees paub tag nrho. Peb cov chaw tsim khoom yog GMP- ntawv pov thawj thiab ua tau raws li US -FDA, EU-GMP, thiab CFDA cov qauv. Qhov no ua kom paub tseeb tias txhua pawg yog ntau dua 98% ntshiab. Peb muaj kaum ob xyoos ntawm kev paub hauv tshuaj synthesis thiab tshuaj intermediates. Txhawm rau pab nrog koj cov kev tshawb fawb thiab kev txhim kho, peb muab cov ntaub ntawv pov thawj kev soj ntsuam tag nrho, suav nrog HPLC thiab cov ntaub ntawv loj spectrometry.
Peb qhov kev mob siab rau mus dhau qhov tsuas yog muab cov khoom zoo - zoo. BLOOM TECH muaj tus nqi tsim nyog nrog cov nqi tsim nyog, kev tswj xyuas cov khoom lag luam txhim khu kev qha uas ua kom cov khoom lag luam ib txwm muaj, thiab kev pabcuam kev tshaj lij los ntawm peb pab pawg R & D. Txawm hais tias koj xav tau me me rau kev kawm lossis ntau ntawm lawv rau kev tsim khoom, peb txoj kev hloov pauv kom haum rau txhua qhov ntau thiab tsawg, los ntawm lab- nplai mus rau kev tsim khoom lag luam.
Peb paub tias nws tseem ceeb npaum li cas los ua raws li cov cai thiab khaws cov ntaub ntawv. Txhua qhov kev xa khoom tuaj nrog cov ntaub ntawv ntxaws ntxaws ntawm kev tshuaj xyuas, cov ntaub ntawv ntawm kev ruaj ntseg, thiab cov ntaub ntawv txhawb nqa kev cai lij choj uas ua kom tshem tawm cov kev lis kev cai yooj yim dua. Peb tus qauv - nres qhov kev pabcuam ua rau kev yuav khoom yooj yim dua, yog li koj tuaj yeem tsom mus rau kev siv koj cov tshuaj kho kom zoo dua thaum peb saib xyuas cov khoom siv nyuaj.
Hu rau peb pab neeg hnub no ntawmSales@bloomtechz.comlos tham txog koj GS-441524 hmoov yuav tsum. Kev paub qhov txawv nrog BLOOM TECH: qhov zoo uas koj tuaj yeem tso siab rau, kev pabcuam uas mus rau saum toj thiab dhau mus, thiab kev sib raug zoo uas txhawb koj txoj kev vam meej hauv kev tshawb fawb thiab kev loj hlob.
Cov ntaub ntawv
1. Murphy BG, Perron M, Murakami E, et al. Cov nucleoside analog GS-441524 muaj zog tiv thaiv kab mob feline infectious peritonitis (FIP) hauv cov ntaub so ntswg kab lis kev cai thiab kev tshawb nrhiav kab mob miv. Veterinary Microbiology. 2018; 219:226-233.
2. Warren TK, Jordan R, Lo MK, et al. Kev kho tau zoo ntawm lub me me molecule GS-5734 tiv thaiv tus kab mob Ebola hauv rhesus liab. Xwm . 2016;531(7594):381-385.
3. Sheahan TP, Sims AC, Graham RL, et al. Dav -spectrum antiviral GS-5734 inhibits ob qho tib si kis mob thiab zoonotic coronaviruses. Science Translational Medicine. 2017;9(396): eaal3653.
4. Gordon CJ, Tchesnokov EP, Woolner E, et al. Remdesivir yog ib qho ncaj qha - ua yeeb yam tshuaj tiv thaiv kab mob uas inhibits RNA- nyob ntawm RNA polymerase los ntawm tus mob ua pa nyuaj rau tus mob coronavirus 2 nrog lub zog siab. Phau ntawv Journal of Biological Chemistry. 2020;295(20):6785-6797.
5. Pedersen NC, Perron M, Bannasch M, et al. Kev ua tau zoo thiab kev nyab xeeb ntawm nucleoside analog GS-441524 rau kev kho cov miv nrog ib txwm tshwm sim feline kis kab mob peritonitis. Phau ntawv Journal of Feline Medicine and Surgery. 2019;21(4):271-281.
6. Agostini ML, Andres EL, Sims AC, et al. Coronavirus cuam tshuam rau cov tshuaj tiv thaiv kab mob remdesivir (GS-5734) yog kho los ntawm tus kab mob polymerase thiab cov ntawv pov thawj exoribonuclease. mBio. 2018;9(2):e00221-18.